Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00114081" target="_blank" >RIV/00216224:14740/20:00114081 - isvavai.cz</a>
Result on the web
<a href="https://www.cell.com/ajhg/pdf/S0002-9297(20)30057-4.pdf" target="_blank" >https://www.cell.com/ajhg/pdf/S0002-9297(20)30057-4.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ajhg.2020.02.015" target="_blank" >10.1016/j.ajhg.2020.02.015</a>
Alternative languages
Result language
angličtina
Original language name
Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures
Original language description
The RNA editing enzyme ADAR2 is essential for the recoding of brain transcripts. Impaired ADAR2 editing leads to early-onset epilepsy and premature death in a mouse model. Here, we report bi-allelic variants in ADARB1, the gene encoding ADAR2, in four unrelated individuals with microcephaly, intellectual disability, and epilepsy. In one individual, a homozygous variant in one of the double-stranded RNA-binding domains (dsRBDs) was identified. In the others, variants were situated in or around the deaminase domain. To evaluate the effects of these variants on ADAR2 enzymatic activity, we performed in vitro assays with recombinant proteins in HEK293T cells and ex vivo assays with fibroblasts derived from one of the individuals. We demonstrate that these ADAR2 variants lead to reduced editing activity on a known ADAR2 substrate. We also demonstrate that one variant leads to changes in splicing of ADARB1 transcript isoforms. These findings reinforce the importance of RNA editing in brain development and introduce ADARB1 as a genetic etiology in individuals with intellectual disability, microcephaly, and epilepsy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
The American Journal of Human Genetics
ISSN
0002-9297
e-ISSN
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Volume of the periodical
106
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
467-483
UT code for WoS article
000523306000005
EID of the result in the Scopus database
2-s2.0-85082433028